Article
Biochemistry & Molecular Biology
Xiaojing Huang, Daniel Winter, Dominic. J. J. Glover, Claudiu. T. T. Supuran, William. A. A. Donald
Summary: Carbonic anhydrases (CAs) are metalloenzymes that play important roles in cellular processes and have been implicated in various diseases. Phosphorylation, a common post-translational modification of CAs, can significantly impact their catalytic activity and drug-binding capabilities. This study highlights the potential regulatory role of phosphorylation in CA activity and its effect on small molecule drug binding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Gayatri Shankar Chilambi, Yu-Hao Wang, Nathan R. Wallace, Chetachukwu Obiwuma, Kirsten M. Evans, Yanhong Li, Menna-Allah W. Shalaby, Daniel P. Flaherty, Ryan K. Shields, Yohei Doi, Daria Van Tyne
Summary: This study identified a mutant strain of Enterococcus faecalis that is hypersusceptible to aminoglycoside antibiotics due to disruption of alpha-carbonic anhydrase (alpha-CA). Disruption of alpha-CA increased proton motive force and membrane permeability, leading to increased gentamicin uptake in E. faecalis. Additionally, an FDA-approved alpha-CA inhibitor sensitized various E. faecalis strains to gentamicin.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Evgenia G. Matveeva, Andrea K. Stoddard, Hui-Hui Zeng, Graham Franke, Leslie Bourne, Carol A. Fierke, Richard B. Thompson
Summary: A novel zinc ion biosensing approach using a carbonic anhydrase-Oplophorus luciferase fusion protein has been described, which employs bioluminescence resonance energy transfer (BRET) to detect zinc ions in solution. This method offers high sensitivity and selectivity, allowing quantitative determination of free zinc ions and detection of their presence through color change in bioluminescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Darya Fayzullina, Semyon Yakushov, Kamilla Kantserova, Elizaveta Belyaeva, Denis Aniskin, Sergey Tsibulnikov, Nafisa Fayzullina, Stanislav Kalinin, Olga Romantsova, Peter S. Timashev, Brett A. Schroeder, Ilya V. Ulasov
Summary: This study discovered that carbonic anhydrase II (CAII) inhibitors can inhibit the growth and invasion of Ewing sarcoma (ES) cells through multiple mechanisms, trigger cell death, and have potential therapeutic effects. The results suggest that cytosolic CAII may be a promising target for ES treatment, and CAII inhibitors can be considered as potential single-agent or combination antitumor agents in the treatment of ES.
Article
Biochemistry & Molecular Biology
Andrea Angeli, Victor Kartsev, Anthi Petrou, Mariana Pinteala, Volodymyr Brovarets, Roman Vydzhak, Svitlana Panchishin, Athina Geronikaki, Claudiu T. Supuran
Summary: A series of novel benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with bulky moieties were synthesized and investigated for their inhibitory effects on various human carbonic anhydrase isoforms. Isoform-selective inhibitors were obtained, with a computational approach employed to explain the observed selectivity, potentially useful in drug design for developing inhibitors with pharmacological applications such as antiglaucoma, diuretic, antitumor, or anti-cerebral ischemia drugs.
Article
Biochemistry & Molecular Biology
Alessio Nocentini, Chad S. Hewitt, Margaret D. Mastrolorenzo, Daniel P. Flaherty, Claudiu T. Supuran
Summary: The study investigated the inhibition of Neisseria gonorrhoeae's alpha-class carbonic anhydrase NgCA by various inorganic and organic anions. The most effective inhibitors were found to be sulfamide, sulfamate, trithiocarbonate, and N,N-diethyldithiocarbamate, showcasing the potential for developing novel antibacterial drugs.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Niccolo Chiaramonte, Andrea Angeli, Silvia Sgambellone, Alessandro Bonardi, Alessio Nocentini, Gianluca Bartolucci, Laura Braconi, Silvia Dei, Laura Lucarini, Elisabetta Teodori, Paola Gratteri, Bernhard Wuensch, Claudiu T. Supuran, Maria Novella Romanelli
Summary: Targeting carbonic anhydrases is a strategy for treating various diseases. In this study, a new series of chiral piperazine compounds was synthesized to widen the structure-activity relationships of potent human carbonic anhydrase inhibitors. Some of the synthesized compounds showed high inhibitory activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Simon L. Durr, Andrea Levy, Ursula Rothlisberger
Summary: The authors propose a model based on 3D convolutional networks to predict the location of zinc in experimental and computationally predicted structures. This study is important because it improves the accuracy of zinc ion location prediction in protein structures.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Linda J. Urbanski, Andrea Angeli, Vesa P. Hytonen, Anna Di Fiore, Giuseppina De Simone, Seppo Parkkila, Claudiu T. Supuran
Summary: Sulphonamides have been found to effectively inhibit the TvaCA1 enzyme, suggesting a potential new approach for combating trichomoniasis. Acetazolamide and ethoxzolamide were identified as the most effective inhibitors, while other sulphonamides tested showed weaker inhibition or were not efficient in inhibiting TvaCA1.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Chad S. Hewitt, Alessio Nocentini, Clemente Capasso, Gabriele Costantino, Daniel P. Flaherty, Claudiu T. Supuran
Summary: The inhibition of alpha-class carbonic anhydrases (CAs) from bacterial pathogens by phenols and phenolic acids was investigated. Small changes in the phenol scaffold led to drastic effects on the inhibitory activity of bacterial CA. This underinvestigated class of bacterial CA inhibitors may have potential in fighting drug resistant bacteria.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Samar A. El-Kalyoubi, Ehab S. Taher, Tarek S. Ibrahim, Mohammed Farrag El-Behairy, Amany M. M. Al-Mahmoudy
Summary: A series of quinoline-uracil hybrids were synthesized and studied for their inhibitory activity and selectivity against multiple enzyme isoforms. Compound 101 showed the best performance in terms of inhibitory activity and selectivity.
Article
Biochemistry & Molecular Biology
Hossam Nada, Ahmed Elkamhawy, Magda H. Abdellattif, Andrea Angeli, Chang Hoon Lee, Claudiu T. Supuran, Kyeong Lee
Summary: In this study, a series of 4-anilinoquinazoline-based benzenesulfonamides were designed and synthesized as potential carbonic anhydrase inhibitors (hCAIs). These compounds showed high inhibitory activity and have potential applications in the treatment of epilepsy, glaucoma, and cancer.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Suleyman Akocak, Nebih Lolak, Simone Giovannuzzi, Claudiu T. Supuran
Summary: This research introduces a series of compounds that exhibit significant inhibitory activity against tumor-associated isoforms of carbonic anhydrase, with certain selectivity. Investigating the structure-activity relationships of these compounds could provide insights for the development of novel therapeutic agents targeting hypoxic tumors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Geochemistry & Geophysics
Ellen K. Olsen, James M. Watkins, Laurent S. Devriendt
Summary: Background electrolytes can affect the precipitation and dissolution rates of calcite, potentially impacting the kinetic isotope fractionation between calcite and dissolved inorganic carbon (DIC). In this study, inorganic calcite was grown from NaCl-CaCl2 solutions to examine the effects of ionic strength on the oxygen isotope fractionation. The results showed no significant ionic strength effect on the fractionation. However, at NaCl concentrations above 0.35M, the isotopic equilibrium between DIC and water could not be maintained due to the inhibitory effect of NaCl on the enzyme carbonic anhydrase. The efficacy of the enzyme decreased exponentially with increasing NaCl concentration. The findings provide insights into oxygen isotope vital effects in marine organisms.
GEOCHIMICA ET COSMOCHIMICA ACTA
(2022)
Article
Chemistry, Physical
Serdar Burmaoglu, Elif Akin Kazancioglu, Mustafa Z. Kazancioglu, Ruya Saglamtas, Gozde Yalcin, Ilhami Gulcin, Oztekin Algul
Summary: This study synthesized new biphenyl-substituted chalcone derivatives and evaluated their inhibitory activity against various enzymes. The results showed that these derivatives exhibited effective inhibition against the enzymes and have potential for the development of new drugs for the treatment of diverse diseases.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Neurosciences
Antonia Gurgone, Riccardo Pizzo, Alessandra Raspanti, Giuseppe Chiantia, Sunaina Devi, Debora Comai, Noemi Morello, Federica Pilotto, Sara Gnavi, Leonardo Lupori, Raffaele Mazziotti, Giulia Sagona, Elena Putignano, Alessio Nocentini, Claudiu T. Supuran, Andrea Marcantoni, Tommaso Pizzorusso, Maurizio Giustetto
Summary: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease without a cure. The study suggests that modulating the activity of mGluR5 receptors may help improve synaptic, functional, and behavioral defects in CDD patients. The findings indicate that mGluR5 receptors could be a potential therapeutic target for CDD.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Laura De Luca, Andrea Angeli, Federico Ricci, Claudiu T. Supuran, Rosaria Gitto
Summary: In recent years, the use of multistep hybrid computational protocols in drug discovery of enzyme inhibitors has gained attention. This study successfully generated pharmacophore models for hCA VA inhibitors using a combination of ligand- and structure-based approaches. Virtual screening on a database of commercially available sulfonamides resulted in the identification of several potential inhibitors.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Vikas Sharma, Rajiv Kumar, Andrea Angeli, Claudiu T. Supuran, Pawan K. Sharma
Summary: In this study, a series of novel 1,2,3-triazole benzenesulfonamide compounds were designed and synthesized, and their inhibitory effects on human carbonic anhydrase were tested. The results showed that these compounds displayed variable inhibition constants against different isoforms of carbonic anhydrase, with some compounds exhibiting strong inhibitory potency. Computational simulations revealed the interactions between these compounds and the binding sites of carbonic anhydrase. The study emphasizes the importance of the synthesized 1,2,3-triazole compounds as building blocks for developing carbonic anhydrase inhibitor drugs.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Annachiara Tinivella, Jerome C. Nwachukwu, Andrea Angeli, Francesca Foschi, Anna Laura Benatti, Luca Pinzi, Tina Izard, Marta Ferraroni, Rangarajan Erumbi, Michael S. Christodoulou, Daniele Passarella, Claudiu T. Supuran, Kendall W. Nettles, Giulio Rastelli
Summary: In this study, a ligand-based and structure-based multi-target repurposing strategy was used to investigate hexahydrocyclopenta[c]quinoline compounds. Human Carbonic Anhydrases (hCA) and Estrogen Receptors (ER) were identified as top candidates for dual modulation. Two new compounds were designed and synthesized, which directly modulate the activities of both hCA and ER. These compounds showed potent inhibition of cancer cell proliferation and selectivity for different cell types. This study lays the foundation for optimizing the multi-target activity of hCA and ER.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emanuela Berrino, Laura Micheli, Simone Carradori, Lorenzo di Cesare Mannelli, Paolo Guglielmi, Alessandro De Luca, Fabrizio Carta, Carla Ghelardini, Daniela Secci, Claudiu T. Supuran
Summary: This study proposes a novel approach to relieve pain in patients with rheumatoid arthritis by combining carbonic anhydrase inhibitors (CAIs) and CO releasing molecules (CORMs). The resulting CAI-CORM hybrids exhibit strong anti-inflammatory effects in in vitro disease models and relieve pain symptoms in an in vivo RA rat model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Andrea Angeli, Laura Micheli, Fabrizio Carta, Marta Ferraroni, Tracey Pirali, Asia Fernandez Carvajal, Antonio Ferrer Montiel, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Claudiu T. Supuran
Summary: We have reported a series of compounds that have the potential to manage oxaliplatin-induced neuropathy (OINP) by modulating human Carbonic Anhydrases (hCAs) and Transient Receptor Potential Vanilloid 1 (TRPV1). These compounds showed effective inhibition activity against the main hCAs involved in OINP in vitro, and some of them exhibited moderate agonism of TRPV1. In vivo evaluation of promising derivatives demonstrated potent and persistent antihypersensitivity effects in a mouse model of OINP.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Simone Carradori, Andrea Angeli, Patrick S. Sfragano, Xheila Yzeiri, Massimo Calamante, Damiano Tanini, Antonella Capperucci, Hannah Kunstek, Mihayl Varbanov, Clemente Capasso, Claudiu T. Supuran
Summary: In this study, new heptamethine-based compounds decorated with a sulfonamide moiety were synthesized for selectively inhibiting bacterial carbonic anhydrases (CAs) and being photoactivated by specific wavelengths. The compounds showed potent CA inhibition and a slight preference for bacterial isoforms. They also exhibited promising effects against S. epidermidis under irradiation, while being non-cytotoxic to human red blood cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shaik Mahammad Ghouse, Kavyaraj Bahatam, Andrea Angeli, Gaurav Pawar, Krishna Kartheek Chinchilli, Venkata Madhavi Yaddanapudi, Arifuddin Mohammed, Claudiu T. Supuran, Srinivas Nanduri
Summary: Carbonic anhydrase isoforms IX and XII play a crucial role in regulating pH in hypoxic tumors and promoting the metastasis of solid tumors. Selective inhibitors targeting these isoforms can reduce their activity, providing an anti-tumor and anti-metastatic mechanism. Coumarin-based derivatives are selective inhibitors of CA isoforms IX and XII. In this study, new 3-substituted coumarin derivatives were designed and synthesized, and their inhibitory activity against various carbonic anhydrase isoforms was evaluated. Tertiary sulphonamide derivative 6c showed selective inhibition against CA IX, while carbothioamides 7c, 7b, and oxime ether derivative 20a exhibited good inhibition against both CA IX and CA XII. The binding mode was predicted and validated using molecular docking and dynamic simulations.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nora Astrain-Redin, Niccolo Paoletti, Daniel Plano, Alessandro Bonardi, Paola Gratteri, Andrea Angeli, Carmen Sanmartin, Claudiu T. Supuran
Summary: In the search for new cancer treatments, organoselenium compounds and carbonic anhydrase inhibitors have shown promise. Selenium-containing compounds, especially selenols, have demonstrated potent inhibition of tumor-associated CA isoforms. In this study, selenoesters combining NSAIDs and natural product fragments were evaluated as nonclassical inhibitors of tumor-associated CA isoforms.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Claudiu T. Supuran
Summary: Carbonic anhydrases play important roles in bacteria and targeting them could lead to the development of novel antibacterials without drug resistance problems. Significant advances have been made in designing effective inhibitors for various bacterial CAs, with in vivo validation for some pathogens.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Chemistry, Medicinal
Lalit Vats, Priyanka Arya, Rajiv Kumar, Simone Giovannuzzi, Neera Raghav, Claudiu T. Supuran, Pawan K. Sharma
Summary: This study synthesized and tested 28 novel compounds for their inhibition potential against cathepsin B and hCA isoforms, and found that one compound exhibited better and more selective inhibition against the cancer-associated hCA IX.
FUTURE MEDICINAL CHEMISTRY
(2023)
Editorial Material
Chemistry, Medicinal
Francesco Fiorentino, Fabrizio Carta, Dante Rotili, Antonello Mai, Claudiu T. Supuran
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anastasija Balasova, Aleksandrs Pustenko, Alessio Nocentini, Daniela Vullo, Claudiu T. Supuran, Raivis Zalubovskis
Summary: A range of 3H-1,2-benzoxaphosphepine 2-oxide aryl derivatives were synthesized in five steps from salicylaldehydes. These compounds showed selective inhibition against cancer-associated CA IX and XII, with the fluorine-containing analogues being the most potent inhibitors. SAR analysis indicated that 7- and 8-substituted aryl derivatives were more effective inhibitors of CA IX and XII than 9-substituted derivatives.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Deepak Shilkar, Mohd Usman Mohd Siddique, Silvia Bua, Sabina Yasmin, Mrunali Patil, Ajay Kumar Timiri, Claudiu T. Supuran, Venkatesan Jayaprakash
Summary: A series of phthalimide-capped benzene sulphonamides (1-22) were evaluated for their inhibitory activity against carbonic anhydrase I (hCA I) and carbonic anhydrase II (hCA II). Compound 1 showed potent inhibitory activity against both hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), with 10 and 6 times higher potency than the standard inhibitor, acetazolamide. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Correction
Biochemistry & Molecular Biology
Mohamed Marzouk, Shimaa M. Khalifa, Amal H. Ahmed, Ahmed M. Metwaly, Hala Sh. Mohammed, Hanan A. A. Taie
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Yong-Si Liu, Ming-Hao Hu
Summary: In this study, a selffolded fluorescent probe was designed to selectively illuminate G4s by unfolding its intramolecular aggregation mediated by G4 binding. This probe showed more controllable background emission and promising ability to track G4 forming dynamics compared to previous disaggregation-induced emission (DIE) probes.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Xiang, Zhuo Yuan, Qichuan Deng, Linshen Xie, Dongke Yu, Jianyou Shi
Summary: This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors for renal fibrosis. Currently, there are no clear therapeutic targets or drugs for renal fibrosis; however, some natural products may have potential efficacy for treating renal fibrosis.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Anna Nikitjuka, Bruna Rafaela Pereira Resende, Michael Smietana, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Summary: Boron-based compounds have been extensively studied in medicinal chemistry, playing a crucial role in designing small molecule drugs for various diseases. Boron is particularly valuable in developing inhibitors for metalloenzymes carbonic anhydrases, and it can modulate ligand recognition ability and selectivity. Recent advancements have led to the discovery of novel boron-based inhibitors that can inhibit carbonic anhydrases through a Lewis acid-base mechanism. Further research is needed to fully explore the potential of boron-based inhibitors and advance their clinical applications.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xinxin Liu, Lei Chen, Ze Chen
Summary: This study developed a nanostructured photosensitizer loaded with oxygen-throttling drug and demonstrated its enhanced cytotoxicity against tumor cells under hypoxic conditions. Animal experiments showed the enhanced tumor targeting capability of the photosensitizer and its inhibitory effect on tumor growth.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Shuai Jiang, Wen-Yan Li, Zai-Feng Yuan, Qin-Shi Zhao
Summary: This study isolated two new dimeric Lycopodium alkaloids and twelve previously undescribed Lycopodium alkaloids from Lycopodiastrum casuarinoides. The structures of these compounds were determined and their inhibitory activities on the Cav3.1 channel were evaluated.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yan Yang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Man Zhang, Jing Liu, Jie Xin, Tao Xu, Wen-Jie Ma, Xiao-Liu Li, Ke-Rang Wang
Summary: In this study, a series of nucleolar fluorescent probes based on naphthalimide derivatives were designed and synthesized, which could achieve clear nucleolar staining in living cells. The results showed that these probes exhibited good targeting to the cell nucleolus and could bind to RNA and enhance fluorescence. This has positive implications for the diagnosis and treatment of nucleolus-related diseases.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yongxi Dong, Fang Wang, Jinlan Wen, Yongqing Mao, Shanhui Zhang, Tiemei Long, Zhangxiang Yang, Lei Li, Jiquan Zhang, Li Dong, Gang Liu, Jianwei Xu
Summary: The hybrid molecules of Scutellarein and Tertramethylpyrazine show excellent neuroprotective and antiplatelet effects in the treatment of ischemic stroke. Compound 1e is particularly effective, enhancing cell membrane permeability and inhibiting cell uptake, as well as significantly reducing cerebral infarction volume.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Chen, Yuanyuan Ying, Jonathan Lalsiamthara, Yuheng Zhao, Saber Imani, Xin Li, Sijing Liu, Qingjing Wang
Summary: This paper examines the role and metabolic regulation of NAD+ in bacteria, highlighting its impact on physiology and virulence. It explores enzymes associated with NAD+ metabolism as potential targets for antibacterial drugs and vaccine candidates. Additionally, it scrutinizes the medical potential of NAD+ and provides insights for its application in biomedicine.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Jon Macicior, Daniel Fernandez, Silvia Ortega-Gutierrez
Summary: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria, is a rare genetic disease that causes premature aging and significantly reduces life expectancy. Currently, there is only one approved drug for treating progeria, but its efficacy is limited. Progerin levels are believed to be the most important biomarker related to disease severity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Fuko Hirano, Naoya Kondo, Yusuke Murata, Aya Sudani, Takashi Temma
Summary: Fluorinated alpha-methyl 3BPA derivatives showed improved water solubility, tumor targetability, and biodistribution compared to 3BPA and BPA, resulting in significantly improved tumor-to-normal tissue ratios.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Ying Shi, Jiaqin Tang, Shumeng Zhi, Ruiqi Jiang, Qing Huang, Lei Sun, Zhizhong Wang, Yanran Wu
Summary: Necroptosis is a type of cell death associated with various diseases. In this study, we identified a small molecule inhibitor, SY-1, that effectively blocks necroptosis by inhibiting the phosphorylation of RIP1/RIP3/MLKL pathway. SY-1 also showed protective effects against TNF-induced hypothermia and improved survival in mice with SIRS. These findings highlight the potential therapeutic applications of SY-1.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Andrea Bagan, Sonia Abas, Judith Pala-Pujadas, Alba Irisarri, Christian Grinan-Ferre, Merce Pallas, Itziar Muneta-Arrate, Carolina Muguruza, Luis F. Callado, Belen Perez, Elies Molins, Jose A. Morales-Garcia, Carmen Escolano
Summary: Recent studies have identified the modulation of imidazoline I-2 receptors (I-2-IR) by selective ligands as a potential strategy for treating neurodegenerative diseases. This study reports a family of bicyclic alpha-iminophosphonates that show high affinity and selectivity for I-2-IR and demonstrates their neuroprotective and anti-inflammatory effects in in vitro and in vivo models. The findings emphasize the importance of exploring structurally novel I-2-IR ligands for therapeutic strategies in neurodegeneration.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)